Formic Acid → HCID 69280851, compound

HRID 1396299Notes

Reaction equation

HRID 1396299 reaction equation
C([N:4]([C:12]1[S:13][C@H:14]2[O:20][C@H:19]([CH2:21][OH:22])[C@@H:18]([O:23][CH2:24][C:25]3[CH:30]=[CH:29][C:28]([O:31][CH3:32])=[CH:27][CH:26]=3)[C@H:17]([O:33][CH2:34][C:35]3[CH:40]=[CH:39][C:38]([O:41][CH3:42])=[CH:37][CH:36]=3)[C@H:15]2[N:16]=1)[C:5](=[O:11])[O:6][C:7]([CH3:10])([CH3:9])[CH3:8])C=C.CCN(CC)CC.C(O)=O.C([O-])(O)=O.[Na+]>O1CCOCC1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.ClCCl>[OH:22][CH2:21][C@H:19]1[O:20][C@H:14]2[C@H:15]([N:16]=[C:12]([NH:4][C:5](=[O:11])[O:6][C:7]([CH3:10])([CH3:9])[CH3:8])[S:13]2)[C@@H:17]([O:33][CH2:34][C:35]2[CH:40]=[CH:39][C:38]([O:41][CH3:42])=[CH:37][CH:36]=2)[C@@H:18]1[O:23][CH2:24][C:25]1[CH:30]=[CH:29][C:28]([O:31][CH3:32])=[CH:27][CH:26]=1

Participants

8

Reactant 4

HCID 284Formic Acid2×HCID 8471TriethylamineHCID 516892Sodium BicarbonateHCID 69084598HCID 69084598, compound

Product 1

HCID 69280851HCID 69280851, compoundYield 65%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of 148 (10.5 g, 18 mmol) in 1,4-dioxane (100 mL) was added Pd(PPh3)4 (4.2 g, 3.6 mmol), Et3N (4.6 g, 45 mmol) and formic acid (4.9 g, 107 mmol) at room temperature under N2 atmosphere. After 20 minutes at 60° C., additional formic acid (24.5 g, 535 mmol) was added. The reaction was stirred at 60° C. for additional 3 hours. Removal of volatiles gave a residue, which was dissolved into dichloromethane (100 mL) and neutralized with saturated aqueous NaHCO3 solution (30 mL). The aqueous layer was extracted with dichloromethane (3×50 mL). The combined organic layer was dried over anhydrous sodium sulfate, and concentrated under vacuum. The residue was purified by flash column chromatography with 10%-50% ethyl acetate in petroleum ether to afford the title compound as a white syrup (6.4 g, 65%). (ES, m/z): [M+H]+ 561.0; 1H NMR (300 MHz, CDCl3) δ 7.30-7.23 (m, 4H), 6.92-6.87 (m, 4H), 6.14 (d, J=6.9 Hz, 1H), 4.56-4.52 (m, 3H), 4.36-4.32 (m, 1H), 4.25-4.19 (m, 1H), 4.13-4.07 (m, 1H), 3.82-3.80 (m, 1H), 3.79 (s, 3H), 3.78 (s, 3H), 3.76-3.51 (m, 3H), 1.54 (s, 9H).

Workup

  1. customRemoval of volatiles
  2. customgave a residue, which
  3. extractionThe aqueous layer was extracted with dichloromethane (3×50 mL)
  4. dry with materialThe combined organic layer was dried over anhydrous sodium sulfate
  5. concentrationconcentrated under vacuum
  6. customThe residue was purified by flash column chromatography with 10%-50% ethyl acetate in petroleum ether

Sources & evidence

ORD record
ord-2f0b203c87a140ba896aa1773991b396
Source dataset
uspto-grants-2014_12
Patent number
US08901087B2

Reaction notes

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